Prioritising respiratory syncytial virus prevention in low-income and middle-income countries
Authors: Xavier Carbonell-Estrany, Eric AF Simões, Louis J Bont, Bosco A Paes, Xavier Carbonell-Estrany, Eric AF Simões, Louis J Bont, Bosco A Paes, Adaeze Ayuk, Angela Gentile, Anne Greenough, Antonio Moreno, Arun Sharma, Asuncion Mejias, Barry Rodgers-Gray, Bernhard Resch, Brigette Fauroux, Carlos E Rodriguez-Martinez, Chadi El Saleeby, W Charles Huskins, Cheryl Cohen, David Greenberg, Eugenio Baraldi, Evan Anderson, Federico Martinon Torres, Fernando F Polack, Giovanni Piedimonte, Harish Nair, Hayley Gans, Heather J Zar, Hiroyuki Moriuchi, Hitoshi Oshitani, Ian Mitchell, D James Nokes, Jarju Sheikh, Jeffrey Pernica, Jesse Papenburg, Joan Robinson, Joanne De Jesus-Cornejo, Joanne Langley, Johannes Liese, Jose Figueras Aloy, Juan Pablo Torres Torretti, Kathryn Edwards, Leonard Krilov, Maduja Divaratne, Manuel Sanchez Luna, Marcello Lanari, Marcelo Scotta, Maria Garba, Masaaki Mori, Merih Cetinkaya, Mitchell Goldstein, Najwa Khuri-Bulos, Nestor E Vain, Nikolaos Papadopoulus, Nusrat Homaira, Octavio Ramilo, Paolo Manzoni, Patrick Munywoki, Pedro A Piedra, Peter Moschovis, Peter Openshaw, Quique Bassat, Renato Stein, Richard Thwaites, Rohitha Muthugala, Rolando Ulloa-Gutierrez, Ron Dagan, Rosa Rodriguez Fernandez, Satoshi Kusuda, Shabir Madhi, Shobha Broor, Simon B Drysdale, Sudha Basnet, Terho Heikkinen, Vasanthi Avadhanula, Xavier Saez-Llorens, Xin Wang, You Li, Joseph L Mathew
Journal: The Lancet Global Health (2023)

Respiratory syncytial virus is a major cause of lower respiratory tract infection morbidity and mortality in children globally, causing 3·2–3·6 million hospitalisations and more than 100 000 deaths annually in children younger than 5 years, 99% of which occur in low-income and middle-income countries (LMICs).1Li Y Wang X Blau DM et al.Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis.Lancet. 2022; 399: 2047-2064Summary Full Text Full Text PDF PubMed Scopus (187) Google Scholar Despite being identified 65 years ago, at the same time as poliovirus, there is no widely available and affordable preventive strategy for respiratory syncytial virus. Over the past few years, the advent of several preventive interventions2PATHRSV vaccine and mAb snapshot.https://www.path.org/resources/rsv-vaccine-and-mab-snapshotDate: January, 2023Date accessed: March 28, 2023Google Scholar finally provides opportunities to address the burden of respiratory syncytial virus disease. A long-acting, single-dose monoclonal antibody that provides season-long protection was approved in Europe in October, 2022.2PATHRSV vaccine and mAb snapshot.https://www.path.org/resources/rsv-vaccine-and-mab-snapshotDate: January, 2023Date accessed: March 28, 2023Google Scholar Additionally, the interim results of phase 2 and phase 3 maternal respiratory syncytial virus vaccine trials for the prevention of severe lower respiratory tract infection caused by respiratory syncytial virus in infants, among whom the burden is greatest, are promising, although the studies await peer review.3PfizerPfizer announces positive top-line data of phase 3 global maternal immunization trial for its bivalent respiratory syncytial virus (RSV) vaccine candidate.https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-data-phase-3-globalDate: Nov 1, 2022Date accessed: March 28, 2023Google Scholar Vaccines for use in early childhood are also under clinical investigation.2PATHRSV vaccine and mAb snapshot.https://www.path.org/resources/rsv-vaccine-and-mab-snapshotDate: January, 2023Date accessed: March 28, 2023Google Scholar However, in the past, new vaccines to prevent important respiratory and diarrhoeal illnesses were authorised and implemented first in high-income countries (HICs) and much later in LMICs. Adoption in LMICs, in our view, lags unacceptably behind. For example, the Haemophilus influenzae type b conjugate vaccine was implemented in LMICs almost 20 years after it was introduced in HICs.4Gavithe Vaccine AllianceHib initiative: a GAVI success story.https://www.gavi.org/news/media-room/hib-initiative-gavi-success-storyDate: 2022Date accessed: March 28, 2023Google Scholar Similarly, the pneumococcal conjugate vaccine, rapidly adopted in HICs, took 15 years to achieve 59% utilisation in middle-income countries.5Tricarico S McNeil HC Cleary DW et al.Pneumococcal conjugate vaccine implementation in middle-income countries.Pneumonia (Nathan). 2017; 9: 6Crossref PubMed Google Scholar Finally, despite the highly successful rotavirus vaccine roll-out in LMICs in 2009, as of January, 2022, it remained unavailable in 21% of African countries and 54% of southeast Asian countries, two regions that account for the majority of rotavirus mortality.6ROTAGlobal introduction status.https://preventrotavirus.org/vaccine-introduction/global-introduction-statusDate: 2022Date accessed: March 28, 2023Google Scholar The disparity in the implementation of highly effective preventive interventions in LMICs, where most mortality from respiratory and diarrhoeal illnesses occurs, is unacceptable and demands urgent concerted action of the global community. This includes the pharmaceutical industry, the UN, public health agencies, foundations, governments and non-governmental organisations, regional and national immunisation technical advisory groups, economists, paediatricians, allied health-care and research personnel, and, importantly, family groups, who strongly advocate for our most vulnerable infants that are least able to advocate for themselves. Several barriers preclude the successful delivery of respiratory syncytial virus preventives in LMICs, including low awareness; a lack of country-specific burden data; logistical, administrative, and structural constraints; and the cost of the products.7Carbonell-Estrany X Simões EAF Bont LJ et al.Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.Front Pediatr. 2022; 101033125Crossref PubMed Scopus (4) Google Scholar, 8WHORSV vaccine research and development technology roadmap.https://www.who.int/publications/i/item/WHO-IVB-17.12Date: Jan 1, 2017Date accessed: March 28, 2023Google Scholar Clearly, the first step must be equitable access to new interventions. Accessibility to respiratory syncytial virus preventives must be streamlined through collaboration, such as that established between the Bill & Melinda Gates Foundation and Pfizer, which will enable faster and more equitable deployment of the maternal respiratory syncytial virus vaccine to LMICs.9Bill & Melinda Gates FoundationBill & Melinda Gates Foundation announces new commitments for vaccine candidates with the potential to reduce newborn and infant deaths in lower-income countries.https://www.gatesfoundation.org/ideas/media-center/press-releases/2022/09/gates-foundation-announces-grants-to-reduce-infant-mortalityDate: Sept 28, 2022Date accessed: March 28, 2023Google Scholar This collaboration is essential to dissolve inequity and accelerate progress. Second, awareness must be increased by disseminating information on the impact of respiratory syncytial virus infection on young children, its manifestations and therapeutic support, and the fundamentals of prevention. Third, it is imperative to address the shortfall in diagnostic tools and clinical resources, particularly the basic need for diagnostic tests to confirm respiratory syncytial virus infection and measure its country-specific impact, and effective oxygen delivery and oximeters. Improved diagnosis is currently supported by WHO and the Gates Foundation. Fourth, the experience, knowledge, and expertise of Gavi, the Vaccine Alliance, and UNICEF, as well as that gained during the COVID-19 pandemic, will be crucial. Fifth, intrinsic to the challenges faced in LMICs is the issue of cost (appendix). Implementing new strategies will have a cost that these countries, undoubtedly, cannot meet alone. A respiratory syncytial virus vaccine price of less than US$5 per dose has been set as a target for LMICs. Importantly, new respiratory syncytial virus preventives involve a single dose (vs three or four doses for pneumococcal conjugate vaccine). In 2011, Gavi successfully negotiated a reduced price of human papillomavirus vaccines via a public–private partnership in LMICs.10Gavithe Vaccine AllianceHuman papillomavirus vaccine support.https://www.gavi.org/types-support/vaccine-support/human-papillomavirusDate: 2018Date accessed: March 28, 2023Google Scholar The simultaneously revised and simplified dosing schedule by WHO facilitated roll-out and further reduced overhead costs. Nevertheless, the uptake of human papillomavirus vaccines remains low, highlighting the challenges faced. Finally, the introduction of any new intervention must be preceded by engagement of local communities to determine preferences, understanding, and priorities. We have now reached a pivotal point in respiratory syncytial virus prevention that demands international recognition, collaboration, and full commitment and engagement of key stakeholders to effect change. The new respiratory syncytial virus preventive strategies have the potential to substantially improve child health and reduce morbidity and mortality, but to truly realise their full potential, the outlined barriers in LMICs must be urgently addressed. We put forward that the time to act is now. The first step should be to bring the key stakeholders together to agree on a unified plan of action to finally end the devastating burden of respiratory syncytial virus in children residing in LMICs. XC-E reports consulting fees from AstraZeneca, Novavax, Merck, Regeneron, and Pfizer. EAFS reports honoraria for lectures or presentations from Pfizer and AstraZeneca; and payments to his institution in grants (from AstraZeneca, Merck, Pfizer, Roche, and Johnson & Johnson), in consulting fees (from Merck, Pfizer, Sanofi, Cidara Therapeutics, Adiago Therapeutics, Nuance Pharmaceuticals, Icosavax, Johnson & Johnson, and Sobi), in support for attending meetings (from AstraZeneca), and for participation on a data safety monitoring board or advisory board (from AbbVie, GlaxoSmithKline, and the Bill & Melinda Gates Foundation). BAP reports consulting fees from AstraZeneca and Sanofi; honoraria for lectures or presentations from AstraZeneca and Sanofi; and payment for participation on an advisory board from Sanofi. LJB declares no competing interests. XC-E, EAFS, LJB, and BAP formed the writing committee for this work. Download .pdf (.45 MB) Help with pdf files Supplementary appendix